Predictive Factors of Fatal Bleeding in Pediatric Acute Promyelocytic Leukemia (APL)
DOI:
https://doi.org/10.36283/ziun-pjmd14-2/040Keywords:
Acute Promyelocytic Leukemia, Tretinoin, Hemorrhage, SepsisAbstract
Background: Pediatric APL has a higher bleeding risk but better outcomes. This study aimed to identify predictors of fatal bleeding in pediatric APL to optimize early interventions and improve survival in Pakistan.
Methods: A retrospective study was conducted at the Department of Pediatric Oncology, Combined Military Hospital, Rawalpindi, from January 2013 to December 2023, using census sampling to analyze data from 51 pediatric APL patients (≤18 years) diagnosed and treated during this period. The severity and type of bleeding were classified using standardized bleeding severity scores. The patients were classified in to standard or high risk categories as per total leucocyte count (TLC). The bleeding events and risk factors to fatal bleeding were noted and compared between the two groups using Independent samplest, Mann Whitney U and Chi square tests. Data analysis was performed using SPSS version 25 and p-value ≤ 0.05 considered statistically significant
Results: Fifty-one pediatric APL patients were included with a median age of 4.75 (4.00) years in high-risk group and 10.0 (6.00) years in low risk group (p<0.001). Mortality and fatal bleeding incidence found to be higher in the high-risk group. Fatal bleeding occurred in 8 (28.57%) high risk patients and 6 (26.08%) low risk group which contributed to mortality. Higher median TLC, Partial Thromboplastin Time (PTT) and activated PTT were noticed in patients who suffered from fatal bleeding. Sixteen (31.37%) patients couldn’t survive with 6 (37.5%) patients suffering a fatal bleeding event which led to death
Conclusion: Higher WBCs, lower platelets and prolonged PT / aPTT are potential risk factors of fatal bleeding and mortality in APL patients.
References
Sabljic N, Thachil J, Pantic N, Mitrovic M. Hemorrhage in acute promyelocytic leukemia-fibrinolysis in focus. Res Pract Thromb Haemost. 2024 Jul;8(5):102499. https://doi.org/10.1016/j.rpth.2024.102499
Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): a review of the literature. Oncotarget. 2020 Mar;11(11):992–1003. https://doi.org/10.18632/oncotarget.27540
Klein K, Kaspers G, Harrison CJ, Beverloo HB, Reedijk A, Bongers M, et al. Clinical impact of additional cytogenetic aberrations, cKIT and RAS mutations, and treatment elements in pediatric t(8;21)-AML: Results from an international retrospective study by the International Berlin-Frankfurt-Münster Study Group. J Clin Oncol. 2015 Dec;33(36):4247–58. https://doi.org/10.1200/JCO.2015.62.4117
Andrade FG, Feliciano SVM, Sardou-Cezar I, Brisson GD, dos Santos-Bueno FV, Vianna DT, et al. Pediatric acute promyelocytic leukemia: Epidemiology, molecular features, and importance of GST-Theta 1 in chemotherapy response and outcome. Front Oncol. 2021 Mar;11:642744. https://doi.org/10.3389/fonc.2021.642744
Rasekh EO, Elsayed GM, Madney Y, El Gammal MM. Prognostic significance of bcr-1 and bcr-3 isoforms of PML-RARA and FLT3-ITD in patients with acute promyelocytic leukemia. Clin Lymphoma Myeloma Leuk. 2020 Mar;20(3):156–67. https://doi.org/10.1016/j.clml.2019.12.002
Park KM, Yoo KH, Kim SK, Lee JW, Chung NG, Ju HY, et al. Clinical characteristics and treatment outcomes of childhood acute promyelocytic leukemia in Korea: A nationwide multicenter retrospective study by Korean Pediatric Oncology Study Group. Cancer Res Treat. 2022 Jan;54(1):269–76. https://doi.org/10.4143/crt.2021.064
Mantha S, Tallman MS, Devlin SM, Soff GA. Predictive factors of fatal bleeding in acute promyelocytic leukemia. Thromb Res. 2018 Apr;164 Suppl 1:S98–102. https://doi.org/10.1016/S0049-3848(18)30326-8
Mamo W, Moges A, Yesuf SA, Mohamedsaid A, Arega G. Treatment outcomes of pediatrics acute myeloid leukemia (AML) and associated factors in the country’s tertiary referral hospital, Ethiopia. BMC Cancer. 2024 May;24(1):640. https://doi.org/10.1186/s12885-024-12144-4
Outcomes of Acute Promyelocytic Leukaemia in Paediatric Patients: Insights from a Low-Middle-Income Country. J Coll Physicians Surg Pak. 2024 Aug;34(08):974–80. https://doi.org/10.29271/jcpsp.2024.08.974
Österroos A, Maia T, Eriksson A, Jädersten M, Lazarevic V, Wennström L, et al. A risk score based on real-world data to predict early death in acute promyelocytic leukemia. Haematologica. 2022 Jan;107(7):1528–37. https://doi.org/10.3324/haematol.2021.279982
Aksu T, Fettah A, Bozkaya İO, Baştemur M, Kara A, Çulha VK, et al. Acute promyelocytic leukemia in children: A single centre experience from Turkey. Mediterr J Hematol Infect Dis. 2018 Jul;10(1):e2018045. https://doi.org/10.4084/MJHID.2018.045
Cai P, Wu Q, Wang Y, Yang X, Zhang X, Chen S. An effective early death scoring system for predicting early death risk in de novo acute promyelocytic leukemia. Leuk Lymphoma. 2020 Jul;61(8):1989–95. https://doi.org/10.1080/10428194.2020.1733945
Fontes HMF, de Freitas JP, Oliveira JHV, de Sousa Moraes ÉA, Rego EM, Melo RAM. Causes and risk factors for early death in adult patients with acute promyelocytic leukemia: A real-life experience. Hematol Transfus Cell Ther. 2024 Dec;46 Suppl 6(Suppl 6):S122–8. https://doi.org/10.1016/j.htct.2024.02.004
Wang A, Zhang Z, Zhu T, Liu X, Duan Q. Clinical characteristics and analysis of related factors associated with early death in newly diagnosed patients with acute promyelocytic leukemia. Discov Oncol. 2024 Aug;15(1):375. https://doi.org/10.1007/s12672-024-00754-w
Xiao M, Zhou P, Liu Y, Wei S, Li D, Li W, et al. Predictive factors for differentiating thrombohemorrhagic disorders in high-risk acute promyelocytic leukemia. Thromb Res. 2022 Feb;210:33–41. https://doi.org/10.1016/j.thromres.2021.11.017
Singh C, Karunakaran P, Yanamandra U, Jindal N, Kumar SR, Saini N, et al. Factors associated with thrombo-hemorrhagic deaths in patients with acute promyelocytic leukemia treated with arsenic trioxide and all-trans retinoic acid. Leuk Res. 2023 Nov;134:107392. https://doi.org/10.1016/j.leukres.2023.107392
Naymagon L, Mascarenhas J. Hemorrhage in acute promyelocytic leukemia: Can it be predicted and prevented? Leuk Res. 2020 Jul;94:106356. https://doi.org/10.1016/j.leukres.2020.106356
Song YH, Qiao C, Xiao LC, Zhang R, Lu H. Hyperfibrinolysis is an important cause of early hemorrhage in patients with acute promyelocytic leukemia. Med Sci Monit. 2018 May;24:3249–55. https://doi.org/10.12659/MSM.909618
Li H, Zhang Y, Fan S, Li D, Zhang Q, Fu J, et al. Analysis of early death in critically ill patients with acute promyelocytic leukemia in the HICU. Sci Rep. 2024 Aug;14(1):19987. https://doi.org/10.1038/s41598-024-36802-3
Minamiguchi H, Fujita H, Atsuta Y, Asou N, Sakura T, Ueda Y, et al. Predictors of early death, serious hemorrhage, and differentiation syndrome in Japanese patients with acute promyelocytic leukemia. Ann Hematol. 2020 Dec;99(12):2787–800. https://doi.org/10.1007/s00277-020-04194-5
Chen C, Huang X, Wang K, Chen K, Gao D, Qian S. Early mortality in acute promyelocytic leukemia: Potential predictors. Oncol Lett. 2018 Apr;15(4):4061–9. https://doi.org/10.3892/ol.2018.7825
Jimenez JJ, Chale RS, Abad AC, Schally AV. Acute promyelocytic leukemia (APL): A review of the literature. Oncotarget. 2020 Mar;11(11):992–1003. https://doi.org/10.18632/oncotarget.27540

Downloads
Published
Issue
Section
License
Copyright (c) 2025 Pakistan Journal of Medicine and Dentistry

This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/